5-aminolevulinic acid induced photodynamic reactions in diagnosis and therapy for female lower genital tract diseases

Abstract

Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.

Keywords: 5-aminolaevulinic acid; HPV infection; female lower genital tract diseases; photodynamic diagnosis; photodynamic therapy.

Figure 1

The heme biosynthesis pathway involving 5-ALA and PpIX. The exogenous 5-ALA participates in the biosynthesis of heme with enzymes localized in the cytoplasm and the mitochondrion generating PpIX, which can further be transformed into heme or discharged mainly through ABCG2 transporter.

Figure 2

Mechanisms of 5-ALA mediated photodynamic reactions. Under aerobic conditions, 5-ALA and given wavelength of laser will induce photodynamic reactions including PDD, PDT induced cell death, PDT induced immune reactions, and PDI.